Loss of tRNA 5-methyluridine methyltransferase and pseudouridine synthetase activities in 5-fluorouracil and 1-(tetrahydro-2-furanyl)-5-fluorouracil (ftorafur)-treated Escherichia coli.
Transfer RNAs from Escherichia coli B treated with either 5-fluorouracil or its analog, 1-(tetrahydro-2-furanyl)-5-fluorouracil (ftorafur), contain low levels of 5-fluorouracil, but are grossly deficient in pseudouridine and 5-methyluridine. The enzymes responsible for the formation of these two modified nucleosides, tRNA pseudouridine synthetase and (5-methyluridine)-methyltransferase, show substantially reduced activity levels in extracts from ftorafur- and 5-fluorouracil-treated cells relative to preparations from normal cells. When these tRNA-modifying activities are examined in vitro, both are inhibited by the addition of fluorouridine-containing tRNAs to the reaction mixtures. Pseudouridine synthetase activity shows potent inhibition. These inhibitory properties of fluorouridine-containing tRNAs, plus the inability of tRNA (5-methyluridine)-methyl-transferase to efficiently use fluorouridine-containing tRNAs as substrates, appear to account for the deficiency of 5-methyluridine and pseudouridine in tRNAs from cells containing low levels of 5-fluorouracil.
D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology*; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019751:Intramolecular Transferases; D007700:Kinetics; D011560:Pseudouridine / Q000378:metabolism; D005641:Tegafur / Q000494:pharmacology*; D012359:tRNA Methyltransferases / Q000378:metabolism*
D011560:Pseudouridine; D005641:Tegafur; D012359:tRNA Methyltransferases; C022769:tRNA(uracil-5)-methyltransferase; D019751:Intramolecular Transferases; C023199:tRNA-pseudouridine synthase I; D005472:Fluorouracil